ABSTRACT
Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.
Subject(s)
Humans , Antigens, Neoplasm , Metabolism , Data Analysis , Databases, Genetic , Immunotherapy , Mutation , Genetics , Neoplasms , Genetics , Allergy and Immunology , Tumor Suppressor Protein p53 , Genetics , Urinary Bladder Neoplasms , GeneticsABSTRACT
Objective To analyze the data from Online Mendelian Inheritance in Man (OMIM) to understand more about it, and provide reference to researchers using this database.Methods 19414 mutations which have definite relevant phenotypes from OMIM were obtained, then these mutations with three databases (1000 Genome Project,GO-ESP,ExAC) which record the mutation frequency in different population were compared.Results Most of the phenotype-related mutations from OMIM are rare mutations whose mutation frequency is less than 1%:18866 in 1000 Genome Project, 18981 in GO-ESP, 18979 in ExAC.The number of mutation whose frequency is more than 1% is 548433435 in 1000 Genome Project, GO-ESP, ExAC, respectively.And there are 320 mutations whose frequency is more than 1% in all databases.In all phenotypes, there are 127 polymorphism phenotypes, 584 susceptibility phenotypes, while in 320 ( 1.6%) phenotypes with common mutations, there are 62 polymorphism phenotypes, 88 susceptibility phenotypes and occupies 48.8%, 15.1%, respectively.Conclusion Approximately 97.5% mutations in OMIM are rare mutations.Polymorphism and susceptibility enrich in common mutations, especially in the mutation whose frequency is more than 10%.
ABSTRACT
[Summary] This retrospective analysis showed that the level of apolipoprotein E was significantly higher in diabetic nephropathy group compared with normal albuminuria group [50.4 (40.8,65.9) vs 46.2 (38.6,56.8)mg/L,P＜0.01].Difference in urinary albumin to creatinine ratio (ACR) among the groups based on the tertile of apolipoprotein E were significant (P＜ 0.01).Multiple linear regression analysis demonstrated that apolipoprotein E was independently associated with ACR (β =0.14,P＜0.05).
ABSTRACT
To investigate the effects and the mechanism of visfatin on MIN6 cell signaling pathway and apoptosis induced by palmitate.Human recombinant visfatin promotes protein kinase B (Akt) and extracellularsignal regulating kinase (ERK)1/2 phosphorylation in dose-and time-dependent manner,and prevents MIN6 cell from apoptosis induced by palmitate (P<0.05 or P<0.01).The activation of Akt and ERK1/2 signaling pathway may be one of the molecular mechanisms of visfatin.
ABSTRACT
Objective To investigate the relationship between serum uric acid ( SUA) concentration and urinary albumin excretion rate ( UAER) and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitua (T2DM). Methods The clinical data of 372 patients with T2DM. including 184 males and 188 females, were collected. The correlations between SUA and the other clinical indexes were analysed by Pearson method, and multiple regression analysis was employed to examine the effects of various factors on UAER and CIMT. Results SUA concentration was higher in males than in females with T2DM (P <0. 01). and was positively correlated with UAER both in males and females with T2DM, even after adjustment for the creatinine clearance (r = 0.24, P < 0.01 for males; r = 0. 29, P < 0.01 for females). Positive correlation was found between SUA concentration and CIMT in females (r =0. 29, P < 0. 01). Multiple regression analysis demonstrated that SUA concentration was an independent determinant of UAER for males as well as females (β=0.16, P<0.05 for males; β=0. 20, P < 0. 05 for females), and was also an independent determinant of CIMT for females (β =0.16, P <0.05). Conclusion SUA plays an important role in the progression of diabetic nephropathy and cardiovascular diseases in patients with T2DM. SUA control may provide a novel approach for the treatment of diabetic nephropathy and vascular complications.